Generally in the cardiac operation, an artificial lung of hollow fiber membrane is used as inserted in the extra-corporeal circulatory path for the purpose of leading a patient's blood out of his body, adding oxygen to the blood, and removing carbon dioxide gas from the blood. The hollow fiber membranes available in the artificial lungs of this nature come in the two types, namely the homogeneous membrane and the porous membrane. The homogeneous membrane effects passage of a gas by allowing the molecules of the gas to be dissolved and dispersed in the membrane. A typical example of the homogeneous membrane is silicone rubber, which has been commercialized as MERA SILOX (Senko Ika Kogyo K.K.),for instance. Because of the restriction imposed by the gas permeability, silicone rubber is the only practicable homogeneous membrane known to the art. The silicone rubber membrane, by reason of strength, is not allowed to have a wall thickness less than 100 .mu.m. It, therefore, has limited gas permeability and exhibits particularly poor permeability to carbon dioxide gas. Worse still, the silicone rubber has a disadvantage that it is expensive and deficient in workability.
In contrast, the porous membrane is such that the micropores contained in the membrane are notably large as compared with the molecules of a gas given to be passed and, therefore, the gas passes the micropores in the form of volume flow. Various artificial lungs using microporous polypropylene membranes and other similar porous membranes have been proposed. It has been proposed, for example, to manufacture porous polypropylene hollow fibers by melt spinning polypropylene with a nozzle for the production of hollow fibers at a spinning temperature in the range of 210.degree. to 270.degree. C. at a draft ratio in the range of 180 to 600, then subjecting the spun fibers to a first heat treatment at a temperature of not more than 155.degree. C., stretching the hot spun fibers to an extent in the range of 30 to 200% at a temperature below 110.degree. C., and subjecting the stretched fibers to a second heat treatment at a temperature exceeding the temperature of the first heat treatment and not exceeding 155.degree. C. (Japanese Patent Publication SHO 56(1981)-52,123). In the porous hollow fibers obtained as described above, since the micropores are physically formed by stretching polypropylene hollow fibers, they are linear micropores substantially horizontal to the direction of the membrane thickness. Further, these micropores are formed by producing cracks in the axial direction of hollow fibers in conformity with the degree of stretching, resulting in a cross section of the shape of a slit. Moreover, the micropores continuously run substantially linearly through the membrane and account for a high porosity. The porous hollow fibers described above, therefore, have a disadvantage that they exhibit high permeability to steam and, when used for extracorporeal circulation of blood for a long time, suffer leakage of blood plasma.
As a porous membrane incapable of incurring leakage of blood plasma, a porous polyolefin hollow fiber has been proposed which is produced by mixing a polyolefin, an organic filler uniformly dispersible in the polyolefin while the polyolefin is in a molten state and readily soluble in an extractant to be used later, and a crystalline core forming agent, discharging the resultant mixture in a molten state through annular spinning orifices and, at the same time, introducing inactive gas into the interiors of the hollow threads of the mixture, cooling and solidifying the hollow threads by contact with a cooling and solidifying liquid incapable of dissolving the aforementioned polyolefin, and then bringing the cooled and solidified hollow threads into contact with the aforementioned extractant thereby removing the aforementioned organic filler by extraction from the hollow threads (Japanese Patent Application SHO 59(1984)-210,466,). One version of the aforementioned hollow fiber membrane is obtained by using, as a cooling and solidifying liquid, a cooling and solidifying liquid capable of dissolving the organic filler to be used as desirable for the process; however, this membrane has a small pore density per unit area and possibly offers an insufficient gas-exchange capacity for use in an artificial lung, though it has no possibility of incurring leakage of blood plasma because the pores are small and complicated in shape. There is another possibility that the low molecular component of the polyolefin will mingle into the cooling and solidifying liquid capable of dissolving the organic filler, eventually adhere to the inner wall of the cooling bath, and cause the shape of the hollow fibers to vary with elapse of time.
As an amendment of such drawbacks as mentioned above, there has been proposed a porous polyolefin hollow fiber membrane produced by a process which comprises mixing polypropylene, an organic filler uniformly dispersible in the polypropylene while the polypropylene is in a molten state and readily soluble in an extractant to be used later, and a crystalline core forming agent, discharging the resultant mixture in a molten state through annular spinning orifices thereby forming hollow threads, cooling and solidifying the hollow threads by contact with a liquid of the aforementioned organic filler or a compound similar thereto, and then bringing the cooled and solidified hollow threads into contact with the extractant incapable of dissolving the polypropylene thereby removing the aforementioned organic filler from the hollow threads by extraction (Japanese Patent Application SHO 61(1986)-155,159). The hollow fiber membrane which is obtained by this method is free from the drawbacks enumerated above. During the course of cooling, however, the organic filler or the cooling and solidifying liquid is locally deposited on the outermost surfaces of the hollow fibers which have not yet been thoroughly cooled and solidified, to lower the ratio of distribution of the polypropylene composition on the outermost surfaces and consequently enlarge the pores in the outer surfaces of the hollow fibers and cause the polypropylene to continue in the form of a heavily rugged network. When the hollow fibers of this nature are used in an artificial lung of the type adapted to pass blood inside the hollow fibers and blow an oxygen-containing gas outside the hollow fibers to effect addition of oxygen to the blood and removal of carbon dioxide gas from the blood, no problem is raised. Conversely when the hollow fibers are used in an artificial lung of the type adapted to flow blood outside the hollow fibers and blow an oxygen-containing gas inside the hollow fibers, they entail a disadvantage that the outer surface of the hollow fibers, owing to their quality described above, inflict an injury on the blood cells and aggravate the pressure loss. Further, the artificial lung using such a hollow fiber membrane as described above, without reference to the choice between the two types of artificial lung, has a disadvantage that during the course of assembly of the artificial lung, the individual hollow fibers conglomerate to impair the workability thereof and jeopardize the effect of potting.
Heretofore, various permeable membranes have been adopted for the purpose of separating blood into blood cells and blood plasma. These permeable membranes are used for blood plasma purification aimed at removal of abnormal proteins, antigens, antibodies, and immune complexes in such diseases due to abnormal immunity as systemic lupus erythematosus, rheumatoid arthritis, glomerular nephritis, and myasthenia gravis, for manufacture of blood plasma preparations for component transfusion, and for pretreatment of artificial kidneys, for example. As examples of the permeable membranes heretofore used for the blood plasma separation mentioned above, there can be cited a cellulose acetate membrane (Japanese patent Unexamined Publication SHO 54(1979)-15,476) and a polyvinyl alcohol membrane, a polyester membrane, a polycarbonate membrane, a polymethyl methacrylate membrane, and a polyethylene membrane (Japanese Patent Unexamined Publication SHO 57(1982)-84,702). These permeable membranes are deficient in mechanical strength, porosity, and plasma separating ability. When these permeable membranes are used in the blood plasma separation, owing to the clogging of the micropores therein, the erythrocytes are injured and the components of complement in the blood plasma are activated and the separated blood plasma is seriously injured as the result.
A permeable membrane has been proposed which is produced by mixing a polymer such as a crystalline polyolefin or polyamide which is sparingly soluble in a solvent and is stretchable and a compound partially compatible with the polymer and readily soluble in the solvent, molding the resultant mixture in the form of film, sheet, or a hollow article, treating the shaped article with the solvent, drying the treated shaped article, and then uniaxially or biaxially stretching the dried shaped article to an extent falling in the range of 50 to 15,000% (Japanese Patent Publication SHO 57(1982)-20,970). Since this membrane has been stretched for the purpose of increasing pore diameter, it is susceptible of thermal shrinkage so much that, when the permeable membrane is used in a medical device, it will not be able to be safely sterilized in an autoclave. Moreover since the micropores are formed by stretching in the permeable membrane, they are linear micropores substantially parallel to the direction of thickness of the membrane. Since the micropores have a substantially uniform shape in the opposite surfaces and in the interior of the wall of the membrane, they are inevitably clogged with proteins and blood cells when the permeable membrane is used in the blood plasma separation.
As concerns permeable membranes for use in the blood plasma separation, polyolefin type macromolecules have been attracting attention as materials experiencing activation of complements only to a nominal extent and excelling in bio-adaptability. At present, studies are underway on the feasibility of permeable membranes using such polyolefin type macromolecules. For example, there has been disclosed a method for the production of a porous membrane, which comprises preparing a molten mixture consisting of 10 to 80% by weight of a paraffin and 90 to 20% by weight of a polypropylene resin, extruding the molten mixture through a die in the form of a film, a sheet, or a hollow fiber, suddenly solidifying the molten extruded mixture in water kept at a temperature of not more than 50.degree. C, and then separating the paraffin from the shaped article by extraction (Japanese Patent Unexamined Publication SHO 55(1980)-60,537). The porous membrane which is obtained by this method, however, does not fit speedy blood plasma separation because the membrane has been suddenly cooled with water, a substance of a large specific heat, and, as the natural consequence, the pores formed in the surfaces and those formed in the interior of the membrane have small diameters and the porosity is low and the speed of permeation is proportionately low.
As means of cooling and solidifying the aforementioned molten mixture, there has been proposed a method which uses a metallic roller and a method which uses a cooling and solidifying liquid such as a paraffin possessing highly desirable compatibility with the aforementioned organic filler (Japanese Patent Application SHO 60(1985)-237,069). The former method produces a porous membrane which possesses surface pores of an extremely small diameter and, therefore, passes blood plasma only at a low speed. In the latter method, since the cooling and solidifying liquid has a small specific heat as compared with water and, therefore, promotes the crystallization of polypropylene at a proper cooling rate, the membrane is enabled in the interior thereof to form micropores of a diameter large enough for the purpose of blood plasma separation and is suffered in the surface regions thereof to form a very large reticular structure which is believed to arise because the polypropylene in the surface regions is dissolved out into the cooling and solidifying liquid before it is allowed to solidify. In the porous membrane possessing such surface layers as described above, the surface layers each function as a prefilter. Thus, the porous membrane is capable of carrying out the blood plasma separation at a highly desirable speed without suffering proteins and blood cells to clog the micropores. When this porous membrane is brought into contact with blood, however, it is liable to occlude blood cells, which may possibly be forced to liberate homoglobin under application of pressure.
An object of this invention, therefore, is to provide an improved porous polypropylene membrane and a method for the production thereof.
Another object of this invention, is to provide an improved porous polypropylene hollow fiber membrane, a method for the production thereof, and an artificial lung using the hollow fiber membrane. A further object of this invention is to provide a porous polypropylene hollow fiber membrane possessing a high gas-exchange capacity, a method for the production thereof, and an artificial lung using the hollow fiber membrane. Still another object of this invention is to provide a porous polypropylene hollow fiber membrane which, while being used in an artificial lung of either of the type passing blood inside or the type passing blood outside, induces no leakage of blood plasma and retains a high gas-exchange capacity intact through a protracted service without impairing blood cells or aggravating pressure loss and which, therefore, is useful for an artificial lung, a method for the production thereof, and an artificial lung using the hollow fiber membrane. Yet another object of this invention is to provide a porous polypropylene hollow fiber membrane which possesses a smooth outer surface and defies conglomeration of individual hollow fibers thereof during the course of assembly of an artificial lung, a method for the production thereof, and an artificial lung using the hollow fiber membrane.
Another object of this invention is to provide an improved flat-film type porous polypropylene membrane and a method for the production thereof. A further object of this invention is to provide a flat-film type porous polypropylene membrane to be used for blood plasma separation aimed at separating blood into blood cells and blood plasma and for removal of bacteria from blood and a method for the production thereof. Yet another object of this invention is to provide a flat-film type porous polypropylene membrane which, while being used for blood plasma separation, permits the blood plasma separation to proceed at a high speed, suffers the separated blood plasma to be injured only sparingly, and has little possibility of entailing occlusion of blood cells or hemolysis and a method for the production thereof.